The theme of isolation and alienation is a thread running throughout the book.

Isolation in Capetown drives the Vroom family to religious hypocrisy and sexual immorality. Isolation on St. Helena drives Nevil Maskelyne to eccentricity and paranoia. Isolation on the frontier drives settlers like the Paxton brothers to violence and depravity.

Journeys are also a major theme. During the course of their journeys to three continents, Mason and Dixon encounter different cultures, new foods, poems, and music sung by sailors, workers, and famous people. It is "like a stew being stirred around," says Dixon. They encounter many political, scientific, and religious arguments. However, none of these journeys resolve personal conflicts that confound Mason or Dixon.

Another theme is that of boundaries.

The Visto, or Mason Dixon line, between Pennsylvania and Maryland creates an unnatural boundary, as opposed to the natural boundaries of mountains and rivers. Even as the...